Human blood serum and plasma contain a wealth of information relating to disease status and have received significant attention as a source of potential diagnostic markers, especially within the last decade (1, 2). Biomarkers include a broad spectrum of proteins (3-7) and peptides (8-10). One such peptide found in blood is fibrinogen peptide A (fibrinopeptide A or FPA), the level of which has been correlated to several diseases including urothelial cancer (11), ovarian cancer (12), gastric cancer (13), and hepatocellular carcinoma (14). The discovery of disease markers in blood fluid continues to accelerate as proteomics technology becomes both more powerful and more widely available (16-17).
Preanalytical variability is a particularly complex issue in protein biomarker discovery, especially with blood samples (24-26). A freshly drawn blood sample is a living tissue, filled with a wide range of naturally active and ex vivo activated biochemical pathways, which may alter or destroy protein and peptide content in the sample. Some of the blood enzymes (e.g., proteases) are known to be involved in biochemical processes, such as the protease cascade responsible for coagulation (27). The functions of other enzymes remain to be elucidated.
Currently, a simple, cost-effective, reproducible and accurate method of measuring the information in human serum and plasma is desired. Additionally, a method of using the discovery of markers in bodily fluids, especially blood fluid, to more accurately diagnose prognostic conditions and disease status is desired.